multicellular organisms sense zinc and consequently regulate zinc transport is largely unknown. The main goal of our research is to understand how a family of cell wall-associated receptor kinases (WAK) and WAK-like (WAKL) kinases function in cell-cell and cell-environment communications. We have discovered that WAKL4, a WAK/WAKL family member, plays a critical role in Arabidopsis zinc sensing. Our objective in this application is to elucidate the mechanisms of how plants use WAKL4 to monitor extracellular zinc conditions and to regulate zinc transport. Our central hypothesis is that WAKL4, as a receptor kinase, is one of the key regulatory components in zinc signaling. We propose to test this hypothesis to identify key regulators in Arabidopsis zinc signaling. In Aim 1, we will test if zinc-induced tissue-specific WAKL4 expression plays a role in zinc sensing and zinc transport by identifying the actual components that control zinc-induced WAKL4 expression. A combination of biochemical, genetic and bioinformatic approaches will be used to identify and to determine the roles of the regulatory components. In Aim 2, we will use suppressor screening to identity other critical genes in the WAKL4- mediated zinc signaling. The genetic screening is based on the fact that in the absence of WAKL4, zinc transporter genes fail to respond to external zinc depletion. We will identify mutants whose zinc transporter genes, in absence of WAKL4, remain responding to zinc deficiency. WAKL4 is the first receptor kinase suggested as having a role in mineral sensing and regulation. Our proposed studies are expected to provide critical information in understanding how Arabidopsis uses receptor kinases to sense and respond to zinc, and to significantly advance the understanding of how WAK/WAKL members communicate between the extracellular and intracellular compartments. Relevance to Public Health: Zinc is an essential micronutrient for all organisms and its deficiency is a well-known human-health problem. Our contribution here is expected to be a detailed understanding of how an extracellular matrix-linked receptor kinase plays a role in plant zinc sensing and transport. This contribution is expected to provide the knowledge needed to significantly improve edible plants as better dietary zinc sources for both animals and humans.